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P2X7 Receptor (P2X7R) of Microglia Mediates Neuroinflammation by Regulating (NOD)-Like Receptor Protein 3 (NLRP3) Inflammasome-Dependent Inflammation After Spinal Cord Injury

Xiao Fan, Wei Ma, Yingyu Zhang, Li Zhang

Qingdao Municipal Hospital, Qingdao, Shandong, China (mainland)

Med Sci Monit 2020; 26:e925491

DOI: 10.12659/MSM.925491

Available online: 2020-07-30

Published: 2020-09-21

BACKGROUND: Microglia participate in mediating neuroinflammation in which P2X7R triggered by adenosine triphosphate has a critical effect after spinal cord injury. However, how the P2X7R of microglia regulate neuroinflammation after spinal cord injury is still unclear.
The aim of this study was to explore the mechanism by which the P2X7 receptor of microglia regulates neuroinflammation after spinal cord injury in NLRP3 inflammasome-dependent inflammation.
MATERIAL AND METHODS: Sixt rats were divided into 5 groups: a sham group, a model group, a BzATP group, an A-438079 group, and a BzATP+CY-09 group. Rats in the sham group were only subjected to laminectomy and rats in the other groups were subjected to spinal cord injury followed by treatment with physiological saline, BzATP, A-438079, and BzATP following CY-09, separately. Real-time polymerase chain reaction, Western blot, immunofluorescence staining, and enzyme-linked immunosorbent assay were used to analyze the scientific hypothesis.
RESULTS: (i) P2X7R of microglia was upregulated and downregulated by BzATP, and A-438079 was upregulated after spinal cord injury. (ii) Upregulation of P2X7R on microglia is coincident with increase of neuroinflammation after spinal cord injury. (iii) P2X7R of microglia participates in spinal cord-mediated neuroinflammation via regulating NLRP3 inflammasome-dependent inflammation.
CONCLUSIONS: P2X7R of microglia in spinal cord mediates neuroinflammation by regulating NLRP3 inflammasome-dependent inflammation after spinal cord injury.

Keywords: Inflammasomes, Microglia, neurogenic inflammation, Receptors, Purinergic P2X7, Spinal Cord Injuries